(1) Field of the Invention
This invention relates in general to a method for the treatment of postmenopausal disorders. In one aspect, this invention is directed to a method for the treatment of postmenopausal disorders which employs a unique sequence of administering an estrogen such as estradiol valerate and a progestogen such as medroxyprogesterone acetate. In a further aspect, the invention relates to estrogen-progestogen treatment in climacterium wherein the undesirable symptoms are eliminated or markedly reduced.
(2) Description of the Related Art
It has been observed that with the aging population the number of postmenopausal women in the world has been steadily increasing. For example, in Finland where the present invention originated, out of a population of approximately 5,000,000 there are about 500,000 postmenopausal women. Many of these women require postmenopausal hormones. For postmenopausal hormone substitution, estrogens are currently the drugs of choice, because in addition to eliminating the climacteric symptoms they correct the metabolic adverse effects related to estrogen deficiency. Recently, interest has also been shown towards prophylactic treatment of osteoporosis by estrogen substitution.
Prior to the present invention conventional preparations for the treatment of postmenopausal symptoms were administered in one month regimens to mimic the rhythm of the normal menstrual cycle. One such preparation is a sequentially administered estrogen-progestogen preparation developed by Orion Pharmaceutica of Espoo, Finland and sold under the tradename "Divina". This preparation has been found to be particularly effective for the treatment of postmenopausal symptoms. It contains estradiol valerate (E.sub.2 V) 2 mg and medroxyprogesterone acetate (MPA) 10 mg. MPA was chosen as the preferred progestogen component because it does not decrease the HDL cholesterol level. Since HDL cholesterol evidently has an antiatherosclerotic effect it was assumed that the choice of progestogen is important in long-term use. Apart from that, MPA is well tolerated. In studies Divina has been shown effective and well tolerated by postmenopausal women.
Hirvonen et al disclosed in an article published in the New England Journal of Medicine, Mar. 5, 1981, the effect of different estrogen/progestogen combinations on lipoprotein metabolism in postmenopausal women. This treatment also employs a 1-month regimen.
Although the administration of such preparations as a 1 month cyclic regimen is well known and routinely used, it is also
known that a prolonged administration of unopposed estrogens causes hyperplasia of the endometrium, and thus an increased risk of cancer. These negative effects of the estrogen treatment are overcome by administration of progestins, that prevents the development of hyperplasia and cause withdrawal bleeding.
Moreover, many of the patients receiving such preparations find the experience of withdrawal bleedings every four weeks when normal menstruation bleedings have stopped, very undesirable and feel the possible exacerbation of postmenopausal symptoms during the tablet free weeks inconvenient. Such complaints can in due course lead to decreased patient compliance.
It has now been found that estrogen valerate can be administered safely for a three month period as opposed to the usual one month period without causing endometrial hyperplasia and wherein certain other positive effects are obtained as hereinafter indicated. Accordingly, one or more of the following objects can be achieved by the practice of the present invention.
It is an object of the present invention to provide a novel method for the treatment of postmenopausal disorders. Another object of the invention is to provide a method for administering to a woman an estrogen and progestogen compound over a 90 days period in accordance with a prescribed regimen. Another object is to provide a method for administering to a woman estradiol valerate in single, oral daily dose form. A still further object is to provide a method for the administering to a woman medroxyprogesterone acetate in single, oral daily dose form for a specified period which overlaps a certain period during which the estradiol valerate is administered. A further object of this invention is to provide a pharmaceutical kit containing the estrogenic and progesterogenic compounds in successively available unit dose form, including a placebo if desired, for the terminal portion of the treatment period. These and other objects will readily become apparent to those skilled in the art in light of the teachings herein set forth.